Scooby-Doo! Mystery Incorporated is the third Scooby-Doo series produced by Warner Bros. Animation. This marks the first time that the gang has been identified by their group name.

Scooby and the gang make their way to Crystal Cove, a village best by ghouls, poltergeists and other supernatural happenings. Our heroes investigate, but the inhabitants of Crystal Cove don't want their help because the supernatural entities are a main source of cash flow to the city as tourist attractions. The gang's subsequent busting of the fake spook disrupts that local income. And each of the gang's parents don't approve of the other members as well.

In contrast to past Scooby shows, Scooby-Doo! Mystery Incorporated is semi-serialized, as once the episode's mystery is wrapped up, an element introduced early on in the first episode (a pendant with a question mark on it) is re-introduced in subsequent episodes. It is all part of a separate mystery as to the whereabouts of the original Mystery Inc., a gang of teens and their mascot parrot. Another twist is that the gang deals with things that trouble youths, such as relationships, their parents and such. A revolving sub-plot on several episodes had Shaggy forced to choose between being best friends with Scooby or being Velma's boyfriend. Shaggy has since chosen Scooby, leaving Velma broken-hearted.

Velma's parents operate the museum where classic Scooby villains (Miner 49er, Captain Cutler, etc.) are showcased as well as conducting tours, and Fred's dad is the Mayor of Crystal Cove. The city's sheriff, Bronson Stone, would love nothing more than to see the Scooby gang run out of town on a rail, but he is consigned to arrest the perp after the gang busts the mystery.

The gang receives some assistance from an unseen figure who only calls himself "Mister E." It is not clear whether Mister E's motives are for the benefit or hinderance of the gang. They do receive some much needed help from Angel Dynamite, a radio deejay. Mister E has stealthily left clues (the pendant, among other things) and employed others to lead the gang into solving the mystery behind the disappearance of the original Mystery Inc. The mascot of the original team, Professor Pericles, had been committed to an asylum for animals but has since escaped. A missing treasure is also being traced using the missing pieces of a device called the Planispheric Disc which the Conquistadors plotted out before planting them as the assembled device corrupted those near it, but there is concern it could lead to the destruction of Crystal Cove.

Season 1 ended with Fred learning that the Mayor is not his real dad as had been led along all season, but he was trying to find the treasure of Crystal Cove as well. He betrayed Professor Pericles and blackmailed two members of the original team--Brad and Judy Chiles, who had gotten married and bore a child who would become current member Fred Jones whom the Mayor would raise as his own. Fred had proposed marriage to Daphne, but that is on hold as he is on a search to find his parents. Producer Mitch Watson says the series will only have 52 episodes to wrap up all the loose ends, encompassing two seasons.

As season 2 progresses, Fred's real parents--Brad Chiles and Judy Reeves--reappear, but they're actually in the employ of Mister E (Ricky Owens of the original Mystery Inc.) in obtaining the pieces of the Planispheric Disc. The word "Nibiru" plays a part in that it was to signify the collision of Earth with a "Planet X," which was populated by what was the first recorded history of gods. It has also been warned that 500 years ago, the first mystery solvers had a donkey mascot who was corrupted by the search for the treasure and tried to make off with a piece of the Disc but was captured and presumably killed by an alligator. This is first referenced in episode 2 ("Creeping Creatures") and is further enhanced in episode 41, when the spirit of Friar Serra (one of the original mystery solvers) warns Scooby Doo that he will be corrupted and killed by an alligator. A revelation has since arisen as Nova--the cocker spaniel that Brad and Judy had and now Scooby has taken as his girlfriend--becomes the host of the Annunaki, the spirit that can take no physical form and takes the body of animal hosts, and warns Scooby that the treasure is cursed and must be destroyed. In other words, it's not the animal mascot that's being corrupted, it's the humans. The mascot is making off with the disc to destroy it and winds up meeting a deadly fate.

As the series concludes, the gang finds the sarcophagus of Nibiru but refuses to set him free. Professor Pericles does and he is consumed by Nibiru's spirit, turning him into a monster. The gang defeats him by destroying his power source within the tomb, and it creates an alternate timeline in Crystal Cove where everything is pleasant, as the curse had never existed. The gang finds that this timeline is where their mystery-solving exploits actually starts. It ends with Nova, now able to talk like Scooby and Pericles, thanking Scooby Doo for being the bravest dog ever.

In the debut episode, Casey Kasem, who in largest part had been Shaggy's voice (now supplied by Matthew Lillard, who played him the live-action theatrical Scooby films), lends his voice to Shaggy's dad.